US20110144200A1 - Combination of carotenoids and epi-lutein - Google Patents

Combination of carotenoids and epi-lutein Download PDF

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US20110144200A1
US20110144200A1 US12/962,720 US96272010A US2011144200A1 US 20110144200 A1 US20110144200 A1 US 20110144200A1 US 96272010 A US96272010 A US 96272010A US 2011144200 A1 US2011144200 A1 US 2011144200A1
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lutein
epi
carotenoid
subject
plasma
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Thomas Eidenberger
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Gupron GmbH
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Gupron GmbH
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Priority to US12/962,720 priority Critical patent/US20110144200A1/en
Priority to PCT/EP2010/069659 priority patent/WO2011073205A1/en
Priority to CN201080057019.XA priority patent/CN102781435B/zh
Priority to JP2012543694A priority patent/JP5721740B2/ja
Assigned to GUPRON GMBH reassignment GUPRON GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: EIDENBERGER, THOMAS
Publication of US20110144200A1 publication Critical patent/US20110144200A1/en
Priority to US13/896,148 priority patent/US9849178B2/en
Priority to US15/823,195 priority patent/US20180078644A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A61K31/055—Phenols the aromatic ring being substituted by halogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates generally to combinations of epi-lutein with carotenoids, such as of lutein, zeaxanthin and related compositions.
  • Carotenoids are yellow, red and orange pigments that are widely distributed in nature. Although specific carotenoids have been identified in various fruits and vegetables, bird feathers, egg-yolk, poultry skin, crustaceans and macular eye region, they are especially abundant in marigold petals, corn and leafy vegetables. The correlation between dietary carotenoids and carotenoids found in human serum and plasma indicate that only selected groups of carotenoids make their way into the human blood stream to exert their effect.
  • Carotenoids absorb light in the 400-500 nm region of the visible spectrum. This physical characteristic imparts the yellow/red color to the pigments.
  • Carotenoids contain a conjugated backbone composed of isoprene units, which are usually inverted at the center of the molecule, imparting symmetry. Changes in geometrical configuration about the double bonds result in the existence of many cis- and trans-isomers. Mammalian species do not synthesize carotenoids and therefore these have to be obtained from dietary sources such as fruits, vegetables and egg yolks. In the recent years, carotenoids have been attributed several health benefits, which include prevention and or protection against serious health disorders.
  • Carotenoids are non-polar compounds classified into two sub-classes, namely more polar compounds called xanthophylls or oxy-carotenoids and non-polar hydrocarbon carotenes like [beta]-carotene, lycopene, etc. Both the sub-classes have at least nine conjugated double bonds responsible for the characteristic color of the carotenoids.
  • Xanthophylls have ring structures at the end of the conjugated double bond chain with polar functionalities, such as hydroxyl or keto groups. Examples of xanthophylls include lutein, zeaxanthin, capsanthin, canthaxanthin, ⁇ -cryptoxanthin, astaxanthin, etc. As natural colorants and also for their role in human health, xanthophylls containing lutein and zeaxanthin have attracted the renewed attention of scientists and researchers in the biomedical, chemical and nutritional field in recent years.
  • Lutein and zeaxanthin contribute to yellow and orange-yellow color respectively.
  • Lutein and zeaxanthin can be present in plant material in free form (non-esterified) and also as esters.
  • Lutein is present in green leafy vegetables like spinach, kale and broccoli in the free form while fruits like mango, orange, papaya, red paprika, algae and yellow corn. These sources generally contain lutein in the form of its esters etc. Lutein is also present in the blood stream and various tissues in human body and particularly the macula, lens and retina of the eye.
  • lutein esters and lutein in the free form are commercially important nutraceuticals obtained from marigold flowers.
  • lutein esters exist in trans-isomeric form, whereas exposure to heat, light, oxygen, acid, etc. catalyses isomerization from trans- to cis-lutein geometric isomeric forms.
  • the trans-isomeric form of lutein is preferred because of better bio-availability and deeper yellow color compared to the corresponding cis-isomeric form.
  • xanthophylls such as lutein and/or zeaxanthin in human plasma, and especially in the macula lutea.
  • the present invention provides a composition including carotenoids and epi-lutein and methods to increase bioavailability of carotenoids in vivo.
  • the present invention also provides the use of the above composition in foods, beverages, and nutraceuticals.
  • the present invention further provides methods to prevent/treat/improve eye disorders/conditions/diseases, such as age related macular degeneration (AMD), development of cataracts, macular degeneration, pinguecula, etc.
  • AMD age related macular degeneration
  • FIG. 1 shows the degradation of lutein with/without epi-lutein.
  • FIG. 2 shows the degradation of zeaxanthin with/without epi-lutein.
  • FIG. 3 is an HPLC chromatogram of isolated epi-lutein prepared in this application.
  • FIG. 7 are results of comparative plasma levels of lutein and the sum of lutein/epi-lutein after Treatment I and II, respectively.
  • the present invention relates to the combinations of carotenoids, such as lutein and/or zeaxanthin with epi-lutein. It has been surprisingly found that epi-lutein has an effect on the uptake and retention of the carotenoid(s) in blood plasma. Subsequently, the carotenoids are more bioavailable for delivery to macula tissue.
  • carotenoids such as lutein and/or zeaxanthin
  • Carotenoids are a class of hydrocarbons (carotenes) and the corresponding oxygenated derivatives are xanthophylls. They consist of eight isoprenoid units joined in such a manner that the arrangement of isoprenoid units is reversed at the center of the molecule so that the two central methyl groups are in a 1,6-position relationship and the remaining nonterminal methyl groups are in a 1,5-position relationship. All carotenoids may be formally derived from the acyclic C 40 H 56 structure (I) (Compound I), having a long central chain of conjugated double bonds, by (1) hydrogenation, (2) dehydrogenation, (3) cyclization, or (4) oxidation, or any combination of these processes. The class also includes compounds that arise from certain rearrangements or degradations of the carbon skeleton (I) (lycopene), provided that the two central methyl groups are retained.
  • I acyclic C 40 H 56 structure
  • the class also includes compounds that arise from certain rearrangements or degradations of the carbon skeleton
  • carotenoids have been isolated from natural sources. These carotenoids have been listed with their trivial and semisystematic names in Key to Carotenoids (Pfander, 1987) and in the Appendix of Carotenoids, Volume 1A (Kull & Pfander 1995) which also includes literature references for their spectroscopic and other properties.
  • the structure is still uncertain for many of the carotenoids, including stereochemical assignments. In the cases where the structure is uncertain, resolution, followed by structural elucidation with modern spectroscopic methods (including high resolution nuclear magnetic resonance (NMR) spectroscopy) is necessary.
  • NMR nuclear magnetic resonance
  • the name of a specific compound is constructed by adding two Greek letters as prefixes (Compound fragments III) to the stem name carotene.
  • the Greek letter prefixes are cited in alphabetical order noted in compounds IIa.
  • the oxygenated carotenoids most frequently include hydroxy, methoxy, carboxy, oxo, and epoxy functionality.
  • Important and characteristic carotenoids are lycopene (gamma, gamma-carotene) (I), beta-carotene (beta, beta-carotene) (III), alpha-carotene ((6′R)-beta, epsilon-carotene) (IV), beta-cryptoxanthin ((3R)-beta,beta-caroten-3-ol) (V), zeaxanthin ((3R,3′R)-beta, beta carotene-3,3′-diol) (VI), lutein (“xanthophyll”, (3R,3′R,6′R)-beta, epsilon-carotene-3,3′-diol) (VII),
  • Lutein and zeaxanthin are known to comprise the macular pigment and lutein isomerizes into zeaxanthin in the macula.
  • lutein may have a protective effect against cancers of the breast, colon, lung, skin, cervix and ovaries and could bear promise in treatment of cardiovascular disease. Therefore, providing lutein to an individual for use in their diet or as nutritional supplements supports better human health and healthy vision.
  • Epi-lutein ((3R,3′S,6′R)-lutein), also known as 3′-epilutein, is formed by the epimerization of the 3′ hydroxyl from an R configuration to an S configuration.
  • Epi-lutein occurs in nature but only in very minute/trace amounts in very few plants, such as Caltha palustris , several roses and peonies as well as a metabolite of lutein in the human body. Therefore, less than about 1 mg/1 gram of epi-lutein is present in a naturally occurring state of a plant material, more particularly less than about 0.1 mg/gram and most particularly less than about 0.01 mg/gram.
  • Epi-lutein analogs are also included as alternative materials suitable for use as described herein with carotenoids, such as xanthophylls.
  • Such analogs include esters, amides, ethers, silyl ethers, carbonates, carbamates, sulfonates, phosphates, sulfoxides and the like of the hydroxyl groups present in epi-lutein.
  • a group of atoms that, when attached to a reactive functional group in a molecule, mask, reduce or prevent the reactivity of the functional group. Typically, the group may be selectively removed under appropriate conditions.
  • hydroxyl derivatizations include, but are not limited to, those where the hydroxyl group is either acylated (esterified) or alkylated such as benzyl and trityl ethers, as well as alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers (e.g., TMS or TIPPS groups), glycol ethers, such as ethylene glycol and propylene glycol derivatives and allyl ethers.
  • a carotenoid such as a xanthophyll
  • a xanthophyll e.g., lutein, zeaxanthin, ⁇ , ⁇ -carotene, violaxanthin, neoxanthin, astaxanthin, lycopene, canthaxanthin, capsanthin, capsorubin, derivatives thereof including esters, or mixtures thereof
  • increases the plasma uptake of the carotenoid e.g, a xanthophyll such as lutein and/or zeaxanthin.
  • the epi-lutein helps to slow or prevent degradation of the carotenoid so that more of the carotenoid remains in the blood plasma. Consequently, an increased amount of the carotenoid then can be effectively delivered to the macula to help support the health of the tissue as well as treat or prevent possible AMD.
  • Suitable epi-lutein material can be prepared by known methods and those as noted in the Examples contained herein.
  • xanthophyll ester is intended to include the mono or di-esters of “free” xanthophylls and, generally, at least one fatty acid.
  • the plant source contains the xanthophyll in the esterified form as a mono- or di-C12-C18 long chain, fatty acid such as lauric, myristic, oleic, linolenic and/or palmitic acids.
  • Lutein in marigold flowers, zeaxanthin in wolfberries and capsanthin and capsorubin in pepper plants are present as xanthophyll diesters.
  • the free or non-esterified xanthophyll can be found in other plants such as spinach, broccoli, kale and corn.
  • free xanthophyll (or free lutein, etc.) is intended to mean the carotenoid having a hydroxyl portion that remains after hydrolysis of the xanthophyll ester.
  • the purity of the carotenoid content utilized in the present invention is generally at least 90%, more particularly 95%, and even more particularly 99% or better, e.g., 99.5%.
  • the purified xanthophylls of the present invention can be utilized in the treatment of a diseases or conditions noted throughout this specification. They can also be used generally as nutritional supplements.
  • the xanthophylls can be purified.
  • ultrafiltration can be used to remove unwanted components by molecular weight cut offs.
  • the retentate from the filtration can be stored as a liquid or, for example, can then be further concentrated into a powder by spray drying, freeze drying, flash drying, fluidized bed drying, ring drying, tray drying, vacuum drying, radio frequency drying or microwave drying.
  • the product should contain at least 95% by weight xanthophyll content, in particular about 99%, more particularly 99.5% or better.
  • the xanthophylls can be further purified by one or more methods known in the art, such as chromatography, gel chromatography, high performance liquid chromatography, crystallization, affinity chromatography, partition chromatography and the like. Identification of the particular xanthophylls can be accomplished by methods know to those skilled in the art and include 1 H NMR, chemical degradation, chromatography and spectroscopy, especially homo- and heteronuclear two-dimensional NMR techniques for the characterization of the isolated isoprenoid compounds.
  • purified or “isolated” is used in reference to the purification and/or isolation of one or more xanthophylls as described above. Again using conventional methods known in the art, various xanthophylls can be separated into purified materials. In one aspect of the invention, the xanthophylls are substantially purified and isolated by techniques known in the art.
  • the purity of the purified compounds is generally at least about 90%, preferably at least about 95%, and most preferably at least about 99% and even more preferably at least about 99.9% (e.g. about 100%) by weight.
  • the present invention further provides bioavailable isolated xanthophylls described herein in combination with epi-lutein that are useful to treat various afflictions noted herein.
  • the xanthophyll(s) and epi-lutein can be administered by a number of methods, as discussed infra.
  • the xanthophyll(s) and epi-lutein compositions of the invention can be incorporated into various foods, drinks, snacks, etc.
  • the composition can be sprinkled onto a food product, prior to consumption.
  • a suitable carrier such as starch, sucrose or lactose, can be used to help distribute the concentration of the xanthophyll(s) and epi-lutein making it easier to apply to the food product.
  • the xanthophyll(s) and epi-lutein compositions of the present invention can also be provided as supplements in various prepared food products.
  • prepared food product means any natural, processed, diet or non-diet food product to which a composition of the invention has been added.
  • the xanthophyll(s) and epi-lutein compositions of the present invention can be directly incorporated into many prepared diet food products, including, but not limited to diet drinks, diet bars and prepared frozen meals.
  • the xanthophyll(s) and epi-lutein compositions of the inventions can be incorporated into many prepared non-diet products, including, but not limited to candy, snack products such as chips, prepared meat products, milk, cheese, yogurt, sport bars, sport drinks, mayonnaise, salad dressing, bread and any other fat or oil containing foods.
  • snack products such as chips, prepared meat products, milk, cheese, yogurt, sport bars, sport drinks, mayonnaise, salad dressing, bread and any other fat or oil containing foods.
  • food product refers to any substance fit for human or animal consumption.
  • the xanthophyll(s) and epi-lutein compositions of the invention can be added to various drinks, such as fruit juices, milkshakes, milk, etc.
  • the preferred method of administration is oral.
  • the xanthophyll(s) and epi-lutein compositions of the invention can be formulated with suitable carriers such as starch, sucrose or lactose in tablets, capsules, solutions, syrups and emulsions.
  • suitable carriers such as starch, sucrose or lactose in tablets, capsules, solutions, syrups and emulsions.
  • the tablet or capsule of the present invention can be coated with an enteric coating that dissolves at a pH of about 6.0 to 7.0.
  • a suitable enteric coating, which dissolves in the small intestine but not in the stomach, is cellulose acetate phthalate.
  • Formulation of the xanthophyll(s) and epi-lutein compositions of the invention into a soft gel capsule can be accomplished by many methods known in the art. Often the formulation will include an acceptable carrier, such as an oil, or other suspending or emulsifying agent.
  • an acceptable carrier such as an oil, or other suspending or emulsifying agent.
  • Suitable optional carriers include but are not limited to, for example, fatty acids, esters and salts thereof, that can be derived from any source, including, without limitation, natural or synthetic oils, fats, waxes or combinations thereof. Moreover, the fatty acids can be derived, without limitation, from non-hydrogenated oils, partially hydrogenated oils, fully hydrogenated oils or combinations thereof.
  • Non-limiting exemplary sources of fatty acids include seed oil, fish or marine oil, canola oil, vegetable oil, safflower oil, sunflower oil, nasturtium seed oil, mustard seed oil, olive oil, sesame oil, soybean oil, corn oil, peanut oil, cottonseed oil, rice bran oil, babassu nut oil, palm oil, low erucic rapeseed oil, palm kernel oil, lupin oil, coconut oil, flaxseed oil, evening primrose oil, jojoba, wheat germ oil, tallow, beef tallow, butter, chicken fat, lard, dairy butterfat, shea butter or combinations thereof.
  • fish or marine oil sources include shellfish oil, tuna oil, mackerel oil, salmon oil, menhaden, anchovy, herring, trout, sardines or combinations thereof.
  • the source of the fatty acids is fish or marine oil (DHA or EPA), soybean oil or flaxseed oil.
  • beeswax can be used as a suitable carrier, as well as suspending agents such as silica (silicon dioxide).
  • formulations of the invention are also considered to be nutraceuticals.
  • the term “nutraceutical” is recognized in the art and is intended to describe specific chemical compounds found in foods that can prevent disease or ameliorate an undesirable condition.
  • the formulations of the invention can further include various ingredients to help stabilize, or help promote the bioavailability of the components of the beneficial xanthophyll(s) and epi-lutein compositions of the invention or serve as additional nutrients to an individual's diet.
  • Suitable additives can include vitamins and biologically-acceptable minerals.
  • vitamins include vitamin A, B vitamins, vitamin C, vitamin D, vitamin E, vitamin K and folic acid.
  • minerals include iron, calcium, magnesium, potassium, copper, chromium, zinc, molybdenum, iodine, boron, selenium, manganese, derivatives thereof or combinations thereof. These vitamins and minerals can be from any source or combination of sources, without limitation.
  • Non-limiting exemplary B vitamins include, without limitation, thiamine, niacinamide, pyridoxine, riboflavin, cyanocobalamin, biotin, pantothenic acid or combinations thereof.
  • additives can be incorporated into the present xanthophyll(s) and epi-lutein compositions.
  • Optional additives of the present xanthophyll(s) and epi-lutein composition include, without limitation, hyaluronic acid, phospholipids, starches, sugars, fats, antioxidants, amino acids, proteins, flavorings, coloring agents, hydrolyzed starch(es) and derivatives thereof or combinations thereof.
  • antioxidant refers to synthetic or natural substances that prevent or delay the oxidative deterioration of a compound.
  • exemplary antioxidants include tocopherols, flavonoids, catechins, superoxide dismutase, lecithin, gamma oryzanol; vitamins, such as vitamins A, C (ascorbic acid) and E and beta-carotene; natural components such as camosol, camosic acid and rosmanol found in rosemary and hawthorn extract, proanthocyanidins such as those found in grapeseed or pine bark extract, and green tea extract.
  • compositions comprising the xanthophyll(s) and epi-lutein of the invention can be manufactured by methods of conventional mixing, dissolving, granulating, dragee-making levigating, emulsifying, encapsulating, entrapping or lyophilization processes.
  • the compositions can be formulated in conventional manner using one or more physiologically acceptable carriers, diluents, excipients or auxiliaries that facilitate processing of the xanthophyll epi-lutein compositions into preparations that can be used.
  • the xanthophyll(s) and epi-lutein compositions of the invention can take a form suitable for virtually any mode of administration, including, for example, oral, buccal, systemic, injection, transdermal, rectal, vaginal, etc., or a form suitable for administration by inhalation or insufflation.
  • Systemic formulations include those designed for administration by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as those designed for transdermal, transmucosal oral or pulmonary administration.
  • Useful injectable preparations include sterile suspensions, solutions or emulsions of the xanthophyll(s) and epi-lutein compositions in aqueous or oily vehicles.
  • the xanthophyll(s) and epi-lutein compositions can also contain formulating agents, such as suspending, stabilizing and/or dispersing agent.
  • the formulations for injection can be presented in unit dosage form, e.g., in ampoules or in multidose containers, and can contain added preservatives.
  • the injectable formulation can be provided in powder form for reconstitution with a suitable vehicle, including but not limited to sterile pyrogen free water, buffer, dextrose solution, etc., before use.
  • a suitable vehicle including but not limited to sterile pyrogen free water, buffer, dextrose solution, etc.
  • the xanthophyll and epi-lutein compositions can be dried by any art-known technique, such as lyophilization, and reconstituted prior to use.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are known in the art.
  • the xanthophyll(s) and epi-lutein compositions of the invention can take the form of, for example, lozenges, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate).
  • binding agents e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose
  • fillers e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate
  • lubricants e.g., magnesium stearate
  • Liquid preparations for oral administration can take the form of, for example, elixirs, solutions, syrups or suspensions, or they can be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations can be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl p hydroxybenzoates or sorbic acid).
  • the preparations can also contain buffer salts, preservatives, flavoring, coloring and sweetening agents as appropriate.
  • Preparations for oral administration can be suitably formulated to give controlled release of the xanthophyll(s) and epi-lutein composition as is well known.
  • the xanthophyll(s) and epi-lutein compositions can take the form of tablets or lozenges formulated in conventional manner.
  • the xanthophyll(s) and epi-lutein compositions can be formulated as solutions (for retention enemas) suppositories or ointments containing conventional suppository bases such as cocoa butter or other glycerides.
  • the xanthophyll(s) and epi-lutein compositions can be conveniently delivered in the form of an aerosol spray from pressurized packs or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas.
  • a suitable propellant e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas.
  • the dosage unit can be determined by providing a valve to deliver a metered amount.
  • Capsules and cartridges for use in an inhaler or insufflator can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
  • the xanthophyll(s) and epi-lutein compositions can be formulated as a depot preparation for administration by implantation or intramuscular injection.
  • the xanthophyll(s) and epi-lutein compositions can be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, e.g., as a sparingly soluble salt.
  • transdermal delivery systems manufactured as an adhesive disc or patch, which slowly releases the xanthophyll(s) and epi-lutein compositions for percutaneous absorption, can be used.
  • permeation enhancers can be used to facilitate transdermal penetration of the compositions.
  • Suitable transdermal patches are described in for example, U.S. Pat. No. 5,407,713; U.S. Pat. No. 5,352,456; U.S. Pat. No. 5,332,213; U.S. Pat. No. 5,336,168; U.S. Pat. No. 5,290,561; U.S. Pat. No. 5,254,346; U.S. Pat. No. 5,164,189; U.S. Pat. No. 5,163,899; U.S. Pat. No. 5,088,977; U.S. Pat. No. 5,087,240; U.S. Pat. No. 5,008,110; and U.S. Pat. No. 4,921,475.
  • Liposomes and emulsions are well-known examples of delivery vehicles that can be used to deliver xanthophyll(s) and epi-lutein compositions.
  • Certain organic solvents such as dimethylsulfoxide (DMSO) can also be employed, although usually at the cost of greater toxicity.
  • DMSO dimethylsulfoxide
  • the xanthophyll(s) and epi-lutein compositions disclosed herein can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the xanthophyll(s) and epi-lutein compositions.
  • the pack can, for example, comprise metal or plastic foil, such as a blister pack.
  • the pack or dispenser device can be accompanied by instructions for administration.
  • Soft gel or soft gelatin capsules can be prepared, for example, without limitation, by dispersing the formulation in an appropriate vehicle (e.g., rice bran oil, and/or beeswax) to form a high viscosity mixture. This mixture is then encapsulated with a gelatin based film using technology and machinery known to those in the soft gel industry. The capsules so formed are then dried to constant weight. Typically, the weight of the capsule is between about 100 to about 2500 milligrams and in particular weigh between about 1500 and about 1900 milligrams, and more specifically can weigh between about 1500 and about 2000 milligrams.
  • an appropriate vehicle e.g., rice bran oil, and/or beeswax
  • This mixture is then encapsulated with a gelatin based film using technology and machinery known to those in the soft gel industry.
  • the capsules so formed are then dried to constant weight.
  • the weight of the capsule is between about 100 to about 2500 milligrams and in particular weigh between about 1500 and about 1900 milligram
  • the shell when preparing soft gelatin shells, can include between about 20 to 70 percent gelatin, generally a plasticizer and about 5 to about 60% by weight sorbitol.
  • the filling of the soft gelatin capsule is liquid (principally a carrier such as rice bran oil or wheat germ oil and/or beeswax if desired) and can include, apart from the xanthophylls, a hydrophilic matrix.
  • the hydrophilic matrix if present, is a polyethylene glycol having an average molecular weight of from about 200 to 1000.
  • Further ingredients are optionally thickening agents and/or emulsifying agent(s).
  • the hydrophilic matrix includes polyethylene glycol having an average molecular weight of from about 200 to 1000, 5 to 15% glycerol, and 5 to 15% by weight of water.
  • the polyethylene glycol can also be mixed with propylene glycol and/or propylene carbonate.
  • the soft gel capsule is prepared from gelatin, glycerine, water and various additives.
  • the percentage (by weight) of the gelatin is between about 30 and about 50 weight percent, in particular between about 35 and about weight percent and more specifically about 42 weight percent.
  • the formulation includes between about 15 and about 25 weight percent glycerine, more particularly between about 17 and about 23 weight percent and more specifically about 20 weight percent glycerine.
  • the remaining portion of the capsule is typically water.
  • the amount varies from between about 25 weigh percent and about 40 weight percent, more particularly between about 30 and about 35 weight percent, and more specifically about 35 weight percent.
  • the remainder of the capsule can vary, generally, between about 2 and about 10 weight percent composed of a flavoring agent(s), sugar, coloring agent(s), etc. or combination thereof.
  • the water content of the final capsule is often between about 5 and about 10 weight percent, more particularly 7 and about 12 weight percent, and more specifically between about 9 and about 10 weight percent.
  • soft shell gelatin capsule manufacturing techniques can be used to prepare the soft-shell product.
  • useful manufacturing techniques are the plate process, the rotary die process pioneered by R. P. Scherer, the process using the Norton capsule machine, and the Accogel machine and process developed by Lederle. Each of these processes is mature technologies and is all widely available to any one wishing to prepare soft gelatin capsules.
  • Emulsifying agents can be used to help solubilize the ingredients within the soft gelatin capsule.
  • Specific examples of the surfactant, emulsifier, or effervescent agent include D-sorbitol, ethanol, carrageenan, carboxyvinyl polymer, carmellose sodium, guar gum, glycerol, glycerol fatty acid ester, cholesterol, white beeswax, dioctyl sodium sulfosuccinate, sucrose fatty acid ester, stearyl alcohol, stearic acid, polyoxyl 40 stearate, sorbitan sesquioleate, cetanol, gelatin, sorbitan fatty acid ester, talc, sorbitan trioleate, paraffin, potato starch, hydroxypropyl cellulose, propylene glycol, propylene glycol fatty acid ester, pectin, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropy
  • the present invention also provides packaged formulations of the xanthophyll(s) and epi-lutein compositions disclosed herein and instructions for use of the product for appropriate condition(s).
  • the packaged formulation in whatever form, is administered to an individual in need thereof.
  • the dosage requirement is between about 1 to about 4 dosages a day.
  • the present invention describes the preparation, use, manufacture and packaging of the xanthophyll(s) and epi-lutein compositions disclosed herein in soft gelatin capsules for treatment of various conditions, it should not be considered limited to only soft gelatin capsules.
  • Ingestible xanthophyll(s) and epi-lutein compositions disclosed herein can be delivered in traditional tablets, pills, lozenges, elixirs, emulsions, hard capsules, liquids, suspensions, etc. as described above.
  • the xanthophyll(s) and epi-lutein compositions disclosed herein will generally be used in an amount effective to achieve the intended result, for example in an amount effective to treat or prevent the particular related condition being treated.
  • the composition can be administered therapeutically to achieve therapeutic benefit or prophylactically to achieve prophylactic benefit.
  • therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated and/or eradication or amelioration of one or more of the symptoms associated with the underlying disorder such that the patient reports an improvement in feeling or condition, notwithstanding that the patient can still be afflicted with the underlying disorder.
  • administration of a xanthophyll(s) and epi-lutein composition to a patient suffering from pain provides therapeutic benefit not only when the underlying condition is eradicated or ameliorated, but also when the patient reports a decrease in the severity or duration of the physical discomfort associated with the pain.
  • the xanthophyll(s) and epi-lutein composition can be administered to a patient at risk of developing one of the previously described conditions.
  • xanthophyll(s) and epi-lutein composition administered will depend upon a variety of factors, including, for example, the particular indication being treated, the mode of administration, whether the desired benefit is prophylactic or therapeutic, the severity of the indication being treated and the age and weight of the patient, etc. Determination of an effective dosage is well within the capabilities of those skilled in the art.
  • Total dosage amounts of a xanthophyll(s) and epi-lutein composition will typically be in the range of from about 0.0001 or 0.001 or 0.01 mg/kg/day to about 100 mg/kg/day, but may be higher or lower, depending upon, among other factors, the activity of the components, its bioavailability, the mode of administration and various factors discussed above. Dosage amount and interval can be adjusted individually to provide plasma levels of the compound(s) which are sufficient to maintain therapeutic or prophylactic effect. For example, the compounds can be administered once per week, several times per week (e.g., every other day), once per day or multiple times per day, depending upon, among other things, the mode of administration, the specific indication being treated and the judgment of the prescribing physician. Skilled artisans will be able to optimize effective local dosages without undue experimentation.
  • the present invention provides a composition comprising:
  • epi-lutein in an amount greater than a naturally occurring amount present in a carotenoid material and a carotenoid or derivative thereof, including esters thereof.
  • composition of paragraph 1 wherein the carotenoid is lutein, zeaxanthin, ⁇ , ⁇ -carotene, violaxanthin, neoxanthin, astaxanthin, lycopene, canthaxanthin, capsanthin, capsorubin, derivatives thereof including esters, or mixtures thereof.
  • composition comprising:
  • composition of paragraph 3 wherein the carotenoid is lutein, zeaxanthin, ⁇ , ⁇ -carotene, violaxanthin, neoxanthin, astaxanthin, lycopene, canthaxanthin, capsanthin, capsorubin, derivatives thereof including esters, or mixtures thereof.
  • a method to increase the uptake of a carotenoid in a subject's plasma comprising the step of providing any of the compositions of paragraphs 1 through 4 to a subject.
  • a method of therapy or prevention of age-related macular degeneration in a human subject by increasing deposition of yellow macular pigment in the macula of an eye of the subject comprising orally administering to the subject a sufficient amount of epi-lutein to increase the serum concentration of carotenoid(s) in the subject to at least 0.5 ⁇ g/ml and maintain the increased serum carotenoid concentration at or above 0.5 ⁇ g/ml for at least 14 days, and at least until the macular concentration of carotenoid(s) has achieved equilibrium.
  • the method to increase the concentration of carotenoids in a subject's plasma comprising orally administering to the subject a sufficient amount of epi-lutein to increase the serum concentration of carotenoid(s) in the subject's plasma to at least 0.1 ⁇ g/ml.
  • Feeding type intravenous administration
  • Group A 4 mg lutein/Kg body weight
  • Group B (2 mg lutein+2 mg epi-lutein)/Kg body weight
  • Group C 4 mg zeaxanthin/Kg body weight
  • Group D (2 mg zeaxanthin+2 mg epi-lutein)/Kg body weight
  • FIG. 1 shows the degradation of lutein with/without epi-lutein.
  • Line B is lutein with epi-lutein and line A is lutein without epi-lutein.
  • FIG. 2 shows the degradation of zeaxanthin with/without epi-lutein.
  • Line D is zeaxanthin with epi-lutein and line C is zeaxanthin without epi-lutein.
  • Table 1 provided below details pharmacokinetic characteristics of lutein and zeaxanthin with/without epi-lutein.
  • UV-detection 450 nm
  • the optimum sample quantity was about 15 mg.
  • the sample was weighed accurately in a 50 ml volumetric flask and the quantity was noted as W.
  • the sample was dissolved in 20 ml of THF. The volume was brought to 50 ml with ethanol.
  • the solution was mixed well and added to a quartz cell for UV measurement using ethanol for as a reference sample.
  • the optimal wavelength was 446 nm.
  • the absorption A was recorded.
  • UV % (dilution factor*A 446 )/255/W*100%
  • the rat is a common standard rodent species for pharmacology and toxicity studies as well as for pharmacokinetic studies.
  • Animal maintenance Hygiene Optimal hygienic conditions. Animal room Standard Room temperature About 22° C. ⁇ 2° C. Relative humidity About 30%-70%. Light 12 hours light, 12 hours dark, only artificial light from 6 a.m. to 6 p.m. Cages Makrolon cages type III (39 cm ⁇ 23 cm bottom area, 18 cm height) with wire mesh lids, single caging. Food Ssniff maintenance diet for mice and rats R/M-H V-1534-300, ad libitum. Water Tap water, from Macrolon-bottles with stainless steel cannulae or from a watering system, ad libitum.
  • Bedding material Aspen wood chips supplied by ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved. Random samples of the bedding material were analysed for contaminants by the supplier. Changes once a week. Environmental Nibbling wood bricks (10 cm ⁇ 2 cm ⁇ 2 cm) and Enrichment nesting material, both from the same material and source as the bedding material, were offered to the animals once a week. Acclimatisation At least 5 days. Identification Individual labelling with felt-tipped pen on the tail and cage labels. Humane endpoints Moribund animals and animals in severe distress for animals or pain were removed when noticed, euthanised suffering and necropsied.
  • All plasma samples (at least 200 ⁇ L) were be stored deep frozen at ⁇ 30° C. until shipping on dry ice.
  • Treatment I Treatment II (mg/kg BW) (mg/kg BW) Lutein 0.282 0.147 Epi-lutein 0.000 0.135 Zeaxanthin 0.018 0.018 Sum 0.300 0.300 Treatment II Treatment I Lutein + Epi- Lutein Lutein Epi-Lutein Lutein C max 941 939 428 1244 (ng/ml) AUC 0- ⁇ 18149 14341 6286 20627 (ng ⁇ h ⁇ ml ⁇ 1 ) AUC 0-12 h 97 93 37 130 (ng ⁇ h ⁇ ml ⁇ 1 ) 83 45 24 69
  • FIG. 4 the plasma levels of lutein observed on day 7 of treatment I (corresponding to 0.282 mg Lutein/kg BW) and on FIG. 5 the plasma levels of lutein and epi-lutein observed on day 7 of treatment II (corresponding to 0.147 mg lutein and 0.135 mg epi-lutein/kg BW).
  • FIG. 6 provides the plasma levels of lutein observed on day 7 of Treatment I or II, respectively. It should be emphasized that Treatment I and II consisted of 0.282 and 0.147 mg lutein/kg BW, respectively.
  • FIG. 7 provides the plasma levels of lutein observed on day 7 after Treatment I and the sum plasma levels of lutein and epi-lutein observed on day 7 after Treatment II.
  • Treatment II Treatment I Lutein + Epi- Lutein Lutein Epi-Lutein Lutein C max 941 939 428 1244 (ng/ml) AUC 0- ⁇ 18149 14341 6286 20627 (ng ⁇ h ⁇ ml ⁇ 1 ) AUC 0-12 h 9783 9345 3724 13069 (ng ⁇ h ⁇ ml ⁇ 1 ) It should be emphasized that Treatment I consisted of 0.282 mg lutein/kg BW and Treatment II of 0.147 mg lutein+0.135 epi-lutein mg/kg BW.
  • Table 2 provides the main pharmacokinetic parameters observed for lutein and epi-lutein based on a dosing interval ( ⁇ ) of 24 hours and for the first 12 hours after treatment (corresponding to the range with frequent blood sampling).
  • FIG. 8 provides the plasma levels of lutein observed after both treatments corrected for the dose and represent the plasma response to 0.1 mg lutein/kg BW.
  • Table 3 provides the pharmacokinetic parameters for lutein derived from a dose equivalent of 0.1 mg/kg BW administered either as pure compound (Treatment I) or as a mixture together with epi-lutein (Treatment II).
  • FIGS. 9 and 10 provide the comparable plasma levels of 3′-oxolutein and a fragment typical for lutein-diepoxide, respectively.
  • the basal level observed predose to Treatment I was set to 100.
  • the amount of oxidized products of lutein observed in plasma after Treatment II are substantial lower than Treatment I.
  • Less amount of oxidized metabolite after treatment II indicates that epi-lutein has an ability to keep the amount of lutein and epi-lutein (total xanthophylls) in a higher level in plasma or prevents oxidation of lutein/epi-lutein in plasma, which is highly advantageous to human physiology, e.g. eye health.

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US13/896,148 US9849178B2 (en) 2009-12-14 2013-05-16 Combination of carotenoids and epi-lutein
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013009378A1 (en) * 2011-07-13 2013-01-17 University Of Georgia Research Foundation, Inc. Use of xanthophyll carotenoids to improve visual performance and neural efficiency
EP3265069A4 (en) * 2015-03-02 2018-11-07 OmniActive Health Technologies Limited Method for stress management and overall health status improvement and compositions used therein

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016185939A (ja) * 2015-03-27 2016-10-27 ロート製薬株式会社 経口組成物
WO2016157157A1 (en) * 2015-04-02 2016-10-06 Omniactive Health Technologies Limited Methods for prevention and treatment of cardiometabolic syndrome and compositions used therein
PL3225112T3 (pl) * 2016-04-01 2022-01-03 Trioptotec Gmbh Dyspersja fotouczulacza i jej zastosowanie
CN107302925B (zh) * 2016-04-19 2021-08-06 内蒙古伊利实业集团股份有限公司 一种具有改善视力的功能性组合物及其应用
WO2019043723A1 (en) * 2017-08-30 2019-03-07 Tathagata Dutta EMULSIONS FOR OPHTHALMIC ADMINISTRATION OF ANTIOXIDANTS
US11654173B2 (en) * 2018-09-26 2023-05-23 Omniactive Health Technologies Limited Purified xanthophyll composition comprising (trans,R,R)-lutein and(trans,R,R)-zeaxanthin and process for the preparation thereof
CA3118249A1 (en) * 2018-11-05 2020-05-14 Eneos Corporation Composition for increasing retention of carotenoid in blood
CN110720513A (zh) * 2019-11-21 2020-01-24 重庆市科学技术研究院 一种改善视觉功能的紫苏酸奶及其制备方法
CN112426414B (zh) * 2020-12-03 2022-02-08 温州医科大学 一种眼部抗黏连和防蓝光损伤的护理液及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5747544A (en) * 1995-10-31 1998-05-05 Applied Food Biotechnology, Inc. Method of using pure 3R-3'R stereoisomer of zeaxanthin to treat or prevent retinal degeneration in humans
US6420614B1 (en) * 2000-10-10 2002-07-16 Industrial Organica, S.A. De C.V. Process for obtaining 3′-epilutein
US6818798B1 (en) * 2000-05-03 2004-11-16 University Of Maryland, College Park Process for making a (3R,3′R)-zeaxanthin precursor

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5087240A (en) 1983-08-18 1992-02-11 Drug Delivery Systems Inc. Transdermal drug patch with conductive fibers
US4921475A (en) 1983-08-18 1990-05-01 Drug Delivery Systems Inc. Transdermal drug patch with microtubes
US5163899A (en) 1987-03-20 1992-11-17 Drug Delivery Systems Inc. Transdermal drug delivery system
US5312325A (en) 1987-05-28 1994-05-17 Drug Delivery Systems Inc Pulsating transdermal drug delivery system
GB8804164D0 (en) 1988-02-23 1988-03-23 Tucker J M Bandage for administering physiologically active compound
US5008110A (en) 1988-11-10 1991-04-16 The Procter & Gamble Company Storage-stable transdermal patch
US5088977A (en) 1988-12-21 1992-02-18 Drug Delivery Systems Inc. Electrical transdermal drug applicator with counteractor and method of drug delivery
DE69009946T2 (de) 1989-12-04 1994-11-03 Searle & Co System zur transdermalen Albuterol Applikation.
US5352456A (en) 1991-10-10 1994-10-04 Cygnus Therapeutic Systems Device for administering drug transdermally which provides an initial pulse of drug
JPH07502219A (ja) 1991-12-18 1995-03-09 ミネソタ　マイニング　アンド　マニュファクチャリング　カンパニー 多重層型バリアー構造体
ATE132381T1 (de) 1992-01-29 1996-01-15 Voelkl Franz Ski Ballspielschläger, insbesondere tennisschläger
WO2001083414A1 (en) * 2000-05-03 2001-11-08 University Of Maryland, College Park Process for making a (3r,3'r)-zeaxanthin precursor
US7081478B2 (en) * 2001-06-29 2006-07-25 Chrysantis, Inc. Mixed zeaxanthin ester concentrate and uses thereof
AU2003259793A1 (en) * 2002-08-14 2004-03-03 Medical College Of Georgia Research Institute, Inc. Methods and compositions for treatment of macular and retinal disease
CN1481804A (zh) * 2002-12-17 2004-03-17 无锡杰西医药科技有限公司 防治白内障、黄斑变性等眼病的配方及其使用方法
US7781572B2 (en) * 2005-10-05 2010-08-24 Nse Products, Inc. Nanosized carotenoid cyclodextrin complexes
CN101330840A (zh) * 2005-12-20 2008-12-24 爱尔康研究有限公司 用于抑制黄斑变性进展和促进健康视觉的组合物和方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5747544A (en) * 1995-10-31 1998-05-05 Applied Food Biotechnology, Inc. Method of using pure 3R-3'R stereoisomer of zeaxanthin to treat or prevent retinal degeneration in humans
US6818798B1 (en) * 2000-05-03 2004-11-16 University Of Maryland, College Park Process for making a (3R,3′R)-zeaxanthin precursor
US6420614B1 (en) * 2000-10-10 2002-07-16 Industrial Organica, S.A. De C.V. Process for obtaining 3′-epilutein

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Khachik et al. ("The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older." Investigative Ophthalmology and Visual Science 47.12 (2006): 5234). *
Norman et al. (Carotenoids in Health and Disease, 2004, p.262) *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013009378A1 (en) * 2011-07-13 2013-01-17 University Of Georgia Research Foundation, Inc. Use of xanthophyll carotenoids to improve visual performance and neural efficiency
US20170367996A1 (en) * 2011-07-13 2017-12-28 University Of Georgia Research Foundation, Inc. Use Of Xanthophyll Carotenoids To Improve Visual Performance And Neural Efficiency
EP3265069A4 (en) * 2015-03-02 2018-11-07 OmniActive Health Technologies Limited Method for stress management and overall health status improvement and compositions used therein
US10583095B2 (en) 2015-03-02 2020-03-10 Omniactive Health Technologies Limited Method for stress management and overall health status improvement and compositions used therein

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